Linaclotide: new mechanisms and new promise for treatment in constipation and irritable bowel syndrome

Sood, Ruchit; Ford, Alexander C

doi:10.1177/2040622313500110

Cited by 7 publications

(4 citation statements)

References 34 publications

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“…Linaclotide, a guanylate cyclase C agonist, has also recently been approved by the Food and Drug Administration (FDA) as a treatment for irritable bowel syndrome and chronic constipation. Abdominal cramping, discomfort, and diarrhea are the adverse events commonly reported by patients for linaclotide (about 4%) [52, 129, 130]. Finally, several other studies have also demonstrated the effectiveness of the Senna acutifolia plant, but the long-term use of this well-known laxative is not recommended [122].…”

Section: Therapeutic Approaches To Gi Symptomsmentioning

confidence: 99%

Gastrointestinal Dysfunctions in Parkinson’s Disease: Symptoms and Treatments

Poirier

Aubé

Côté

et al. 2016

Parkinson's Disease

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A diagnosis of Parkinson's disease is classically established after the manifestation of motor symptoms such as rigidity, bradykinesia, and tremor. However, a growing body of evidence supports the hypothesis that nonmotor symptoms, especially gastrointestinal dysfunctions, could be considered as early biomarkers since they are ubiquitously found among confirmed patients and occur much earlier than their motor manifestations. According to Braak's hypothesis, the disease is postulated to originate in the intestine and then spread to the brain via the vagus nerve, a phenomenon that would involve other neuronal types than the well-established dopaminergic population. It has therefore been proposed that peripheral nondopaminergic impairments might precede the alteration of dopaminergic neurons in the central nervous system and, ultimately, the emergence of motor symptoms. Considering the growing interest in the gut-brain axis in Parkinson's disease, this review aims at providing a comprehensive picture of the multiple gastrointestinal features of the disease, along with the therapeutic approaches used to reduce their burden. Moreover, we highlight the importance of gastrointestinal symptoms with respect to the patients' responses towards medical treatments and discuss the various possible adverse interactions that can potentially occur, which are still poorly understood.

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Section: Therapeutic Approaches To Gi Symptomsmentioning

confidence: 99%

Gastrointestinal Dysfunctions in Parkinson’s Disease: Symptoms and Treatments

Poirier

Aubé

Côté

et al. 2016

Parkinson's Disease

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“…When compared with placebo, linaclotide yielded excellent results in terms of the reduction in abdominal pain and increase in complete SBMs at 12 weeks after the initial first administration [57]. Furthermore, linaclotide was associated with a significant increase in the average QOL score relative to placebo in a questionnaire-based survey [58].…”

Section: Linaclotidementioning

confidence: 97%

The Management of Constipation: Current Status and Future Prospects

Maruyama¹,

Kamimura²,

Sugita³

et al. 2019

Constipation

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Chronic constipation, a common condition, can have remarkably negative effects on a patient's quality of life. Recent research has identified factors that may influence the prognosis of chronic constipation and suggests the need for adequate therapy. However, the major obstacles in this field were: (1) a small number of therapeutic options, (2) no clear diagnostic criteria, and (3) no effective method to collect information form the patients. These were due to the fact that bowel movement patterns vary widely among individuals, and also the functional constipation, including irritable bowel syndrome, is difficult to be distinguished from the chronic constipation. Recently, it has been demonstrated that the Rome IV diagnostic criteria of functional constipation and the Bristol stool form scale are useful for the objective evaluation and recording of stool. Based on these developments, and the increase of newly developed medicines the therapy for the constipation is significantly changing and therefore, if conventional therapy for chronic constipation is ineffective, switching of medicines is possible. Therefore, clinicians should update the information of these newly developed drugs available in clinics and diagnostic criteria. For this purpose, in this chapter, we have summarized the perspective on the current paradigm of treatment for chronic constipation focusing on recently introduced therapeutic drugs.

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“…It has been approved by the FDA and by the EMA for the treatment of moderate to severe IBS-C in adults. Its action is focused on the increase of fluid secretion, favouring gastrointestinal transit, and has GC-C-mediated analgesic effects[ 81 ].…”

Section: Therapeutic Targets In Constipation-predominant Irritable Bomentioning

confidence: 99%

New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond

Sinagra¹,

Morreale²,

Mohammadian³

et al. 2017

WJG

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Irritable bowel syndrome (IBS) is a chronic, recurring, and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain, distention, and changes in bowel habits. Although there are several drugs for IBS, effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed. Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism, neurohormonal regulation, immune dysfunction, the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS. With regards to therapies for restoring intestinal permeability, multiple studies with prebiotics and probiotics are ongoing, even if to date their efficacy has been limited. In parallel, much progress has been made in targeting low-grade inflammation, especially through the introduction of drugs such as mesalazine and rifaximin, even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs. This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS, most recently developed in preclinical as well as Phase 1 and Phase 2 clinical studies.

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Linaclotide: new mechanisms and new promise for treatment in constipation and irritable bowel syndrome

Cited by 7 publications

References 34 publications

Gastrointestinal Dysfunctions in Parkinson’s Disease: Symptoms and Treatments

Gastrointestinal Dysfunctions in Parkinson’s Disease: Symptoms and Treatments

The Management of Constipation: Current Status and Future Prospects

New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond

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